聚乙二醇化干扰素α-2a联合利巴韦林治疗代偿期丙型肝炎肝硬化患者临床疗效研究*

目的 探讨应用聚乙二醇化干扰素α-2a联合利巴韦林治疗代偿期丙型肝炎肝硬化患者的临床疗效。方法 2003年1月~2016年12月我院就诊的代偿期丙型肝炎肝硬化患者122例,采用随机数字表法分成两组,每组61例。给予对照组常规护肝治疗,给予观察组聚乙二醇化干扰素α-2a联合利巴韦林治疗24~48 w。随访两组24 w。采用实时荧光定量RT-PCR法检测血清HCV RNA,采用全自动生化分析仪检测血生化指标,采用化学发光法检测血清层粘连蛋白（LN）、Ⅲ型前胶原（PC Ⅲ）、透明质酸（HA）,常规使用Fibroscan行肝脏硬度检测（LSM）。结果 在治疗结束时,观察组血清HCV RNA水平为（2.0±0.4） lg IU/ml,显著低于对照组【（3.8±1.3）lg IU/ml,P<0.05】;血清AST和ALT水平分别（46.03±24.05） U/L和（36.32±20.1） U/L,显著低于对照组【（78.7±21.1） U/L和（51.2±20.9） U/L,P<0.05）;观察组血清LN、PCⅢ和HA水平分别为（126.3±29.0）μg/L、（212.3±43.8）μg/L和（211.4±42.0）μg/L,均显著低于对照组【（140.3±32.1）μg/L、（267.5±39.8）μg/L和（329.6±68.4）μg/L,P<0.05】;观察组LSM为（13.6±2.4） kPa,显著低于对照组【（17.6±5.2）kPa,P<0.05】;在随访时发现,观察组血清ALT复常率和持续病毒学应答率（SVR）均显著高于对照组（分别为93.4%对45.9%和72.1%对9.8%,P<0.05）,而疾病进展发生率为3.3%,显著低于对照组的13.1%（P<0.05）。结论 应用聚乙二醇化干扰素α-2a联合利巴韦林抗病毒治疗代偿期丙型肝炎肝硬化患者可显著提高SVR,延缓肝纤维化进展,稳定肝功能指标。     

Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy： A randomized controlled trial

INTRODUCTION Retreatment of hepatitis C patients who relapsed after recombinant interferon (rIFN) monotherapy has a fair rate of success when ribavirin is added to the original protocol. About 30% of patients infected with hepatitis C virus (HCV) genotype…     

Immunogenicity of recombinant hepatitis B vaccine in treatment-naive and treatment-experienced chronic hepatitis C patients： The effect of pegylated interferon plus ribavirin treatment

AIM: To retrospectively evaluate the vaccination-induced anti-HBs seroconversion rates in treatment-naive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment. METHODS: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20 microg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups: Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05). RESULTS: Fifty-eight of 70 group A patients (82.85%), 20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CHC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 (20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%, P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up. CONCLUSION: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.     

Ursodeoxycholic acid exacerbates peginterferon-induced interstitial pneumonia in a patient with hepatitis C

Pegylated interferon alpha combined with ribavirin is currently the standard treatment for hepatitis C virus (HCV) infection. Ursodeoxycholic acid (UDCA) is used as a complementary treatment in patients who are non-responders or who develop severe side effects of this combined therapy. UDCA is generally considered to be a relatively safe drug. However, we recently encountered a patient with chronic hepatitis C in whom interferon-induced interstitial pneumonia was exacerbated by UDCA. This patient responded to initial antiviral therapy with non-pegylated interferon alpha-2b and ribavirin, but hepatitis recurred soon after the end of treatment. A second course of antiviral therapy using peginterferon alpha-2b and ribavirin achieved normalization of serum transaminases and HCV-RNA, but also caused interstitial pneumonia. After discontinuing peginterferon, this side effect was ameliorated. On the other hand, hepatitis relapsed four months later. UDCA treatment was started and serum transaminase levels decreased, but exacerbation of interstitial pneumonia occurred with marked elevation of the serum KL-6 level. To our knowledge, this is the first reported case of peginterferon-induced interstitial pneumonia showing exacerbation due to UDCA therapy.     

Dual chronic hepatitis B virus and hepatitis C virus infection

Dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are common in HBV or HCV endemic areas. However, several clinical and pathogenetic issues remain unresolved. First, clinical and in vitro studies suggest the interactions between two viruses. The dynamics of the interaction in untreated setting versus treated setting and its influence on the long-term outcomes await further studies. A key issue regarding viral interactions is whether modulation of infection occurs in the same dually infected individual hepatocyte of the liver. Clarifying this issue may help to understand the reciprocal interference between HCV and HBV and provide clues for future immunopathogenetic studies. Second, the prevalence and clinical significance of coexisting occult HBV infection in patients with chronic HCV infection need further investigations. Third, combination therapy of peginterferon alfa-2a and ribavirin appears to be just as effective and safe for the treatment of hepatitis B surface antigen (HBsAg)-positive patients chronically infected with active chronic hepatitis C as it is in patients with HCV monoinfection. Nevertheless, one-third of dually infected patients with nondetectable serum HBV DNA-level pretreatment developed HBV reactivation posttreatment. How to prevent and treat this reactivation should be clarified. Furthermore, about 10% of the dually infected patients lost HBsAg. Underlying mechanisms await further investigations. Finally, the optimal treatment strategies for dually infected patients with hepatitis B e antigen-positive chronic hepatitis B should be identified in future clinical trials.     

蒲地蓝联合利巴韦林治疗小儿手足口病疗效观察

目的 观察蒲地蓝联合利巴韦林对手足口病的治疗效果.方法 手足口病患者70例,随机分为两组：治疗组（蒲地蓝联合利巴韦林）和对照组（单用利巴韦林）.观察两组患者的疗效、皮疹完全消失时间、发热消退时间及不良反应.结果 治疗组治愈率及有效率分别为57%、94%,对照组治愈率及有效率分别为43%、86%,两组治愈率及有效率比较差异有统计学意义（均P＜0.05）.治疗组较对照组在手足皮疹消失、口腔皮疹消失及发热消退时间明显缩短,差异有统计学意义（均P＜0.05）.两组患者均未发现明显不良反应.结论 较单用利巴韦林,蒲地蓝联合利巴韦林治疗手足口病明显提高了治愈率,缩短了皮疹完全消失时间及发热消退时间,是治疗手足口病的一种安全、有效的方法.     

利巴韦林喷剂治疗手足口病疗效观察

目的观察利巴韦林喷剂治疗小儿手足口病的临床疗效。方法126例手足口病患儿分为治疗组68例和对照组56例,分别应用利巴韦林喷剂和抗病毒口服液,观察患儿退热时间、主动进食时间、咽峡部溃疡愈合时间以及手足部位皮疹消退时间。结果治疗组患儿退热时间、主动进食时间、咽峡部溃疡愈合时间短于对照组差异均有统计学意义（P〈0.05）,2组手足部位皮疹消退时间比较差异无统计学意义（P〉0.05）。结论利巴韦林喷剂治疗小儿手足口病疗效较好,无明显不良反应,患儿依从性好。     

Sustained virological response to pegylated interferon plus ribavirin leads to normalization of liver stiffness in hepatitis C virus-infected patients

Introduction

Pegylated interferon plus ribavirin (Peg-IFN/RBV) therapy leads to improvements in liver stiffness measurements (LSM) in hepatitis C virus (HCV)-infected patients. However, the rate of LSM return to normal values in response to Peg-IFN/RBV is unclear. Thus, our aim was to assess the probability and factors associated with LSM normalization in HCV-infected patients receiving Peg-IFN/RBV.

Methods

This prospective observational longitudinal study included 160 HCV-infected patients, 111 (69%) with human immunodeficiency virus and receiving Peg-IFN/RBV, with baseline LSM ≥7 kPa. The outcome variable was LSM normalization, i.e. a stable decrease in LSM below 7 kPa after starting Peg-IFN/RBV.

Results

After starting Peg-IFN/RBV, 56 [35%, 95% confidence interval (95% CI): 28–42%] patients showed LSM normalization. The probability of LSM normalization was 21% (95% CI: 13.2–32.4%) at 12 months, and 51.3% (95% CI: 39.9–63.9%) at 24 months after Peg-INF/RBV initiation for individuals with sustained virological response (SVR), and 8.3% (95% CI: 4–16.6%) at 12 months and 11.3% (95% CI: 6–20.7%) at 24 months for those without SVR (p < 0.001). For individuals with LSM ≥7 kPa 24 weeks after the pre-planned end of treatment, LSM normalizations were only observed among those with SVR. Achievement of SVR [Hazard ratio (HR, 95% CI): 6.84 (3.39–13.81)] and lack of baseline cirrhosis [HR (95% CI): 4.17 (1.69–10)] were independently associated with LSM normalization after starting Peg-IFN/RBV.

Conclusions

LSM normalizations during Peg-IFN/RBV treatment are more likely, and occur earlier among patients with SVR. In addition, LSM normalizations continue 24 weeks after the scheduled end of therapy, but only among individuals who reach SVR.     

小柴胡汤联合PEG-IFN-α与RBV治疗慢性丙型肝炎的临床分析

目的：采用随机对照方法观察小柴胡汤联合聚乙二醇干扰素α（Polyethyleneglycol interferonα,PEG-IFN-α）和利巴韦林（Ribavirin,RBV）治疗丙型肝炎的疗效。方法：将79例丙型肝炎患者随机分为两组：对照组39例（常规PEG-IFN-α和RBV治疗）和治疗组40例（小柴胡汤联合PEG-IFN-α和RBV治疗）。观察两组患者治疗前后患者肝功能（ALT、AST、AKP、GGT、A/G、TBIL、DBIL）、丙型肝炎病毒标志物（HCV-RNA定性）的变化,比较两组的疗效差异。结果：与对照组比较,治疗组肝功能指标显著改善（P﹤0.05）,但HCV-RNA转阴率与对照组无显著差异（P〉0.05）。结论：小柴胡汤联合PEG-IFN-α与RBV治疗改善丙型肝炎患者肝功能效果优于对照组,但抗丙肝病毒优势不明显。